This competitive renewal application for the University of Pennsylvania's Paul Calabresi Career Development Award for Clinical Oncology K12 seeks continued support for the training and mentorship of promising young investigators with a commitment to cancer research. Our K12's mission is to identify and train the next generation of outstand translational investigators who are focused on the problem of human malignancies. This program provides the critical protected time, resources, educational experience, and environment necessary to achieve this goal. Our training program is not a stand-alone entity. It is bolstered bu the remarkable physical and human resource and strong institutional commitments of the Perelman School of Medicine of the University of Pennsylvania (UPENN) and Abramson Cancer Center (ACC), along with the Research Institute at the Children's Hospital of Philadelphia (SHOP), the Center for Clinical Epidemiology and Biostatistics, The Wistar Institute, and Institute for Translational Medicine and Therapeutics (ITMAT). In aggregate, these integrated but distinct academic programs provide a synergistic network and a uniquely rich training environment that is replete with a talented and very diverse pool of mentors who have been selected to cover the full translational research spectrum. The supporting infrastructure and the physical facilities create an environment that is designed to nurture and produce superior clinical translational investigators committed to careers in academic medicine with a track record of success that speaks for itself. Over the last five years, we have chosen 14 trainees from a deep pool of applicants fed from the various clinical oncology training programs as well as an increasing number of external candidates solicited by advertisement. The K12 advisory committee selects trainees from this outstanding candidate pool based upon their demonstrated commitment and promise for translational research. Once enrolled, our trainees embark upon a tailored curriculum based on their specific research interests and education, supplemented by didactic coursework and research seminars. The uniqueness of this K12 is that it facilities in a very explicit manner the bench-to-bedside development of novel translational protocols under the mentorship of a senior investigator and/or experienced clinical researcher. Progress of our trainees is closely monitored by a Scholarly Oversight Committee with an individualized plan that is customized for each trainee and by the K12 program's Advisory Committee, which also reviews overall programmatic priorities. We have established high standards and expectations for our research mentors, and they function in the context of a carefully structured, formal mentorship program for the K12 awardees. The program measure success by resulting publications, funding, and most importantly, independent careers in translational cancer research. In this renewal we seek to build on our success in producing the next generation of clinical oncology researchers and extend our training mission with a second training track for translationally minded PhD scientists and nurses. The dual track structure will allow our program to training jointly clinicians interestd in clinical/translational research alongside PhD basic scientist with a primary focus on basic research. It has become increasingly clear that expeditiously bringing laboratory breakthroughs to patients will not occur in the desired time frame unless the efforts of the clinicians and basic scientist are harmonized. In addition, and in recognition that the scope of translational research cancer should be as broad as possible, our K12 advisory committee over the past 5 years gas made a very deliberate effort to incorporate trainees and mentors from all programmatic disciplines in human malignancies. As a result we have mentors and trainees from all of our major disciplines within the field of oncology. Our program's track record speaks to the quality, dedication, and focus of our trainees, mentors and curriculum; over the last ten years, 90% of our trainees have gone on to pursue full-time translational research academic careers, the vast majority of these with independent funding. This reflects the overreaching mission of our K12 program, which is to train promising young researchers in translational and clinical oncology by equipping them with the most sophisticated education possible in basic science and clinical research methodologies and by exposing them to a deed cadre of mentors and role models with proven success in their respective fields. The specialized training support by the crucial grant places our trainees at the leading edge of their respective research areas. It enables them to be ideally situated to compete for further NIH funding and become the future leader and mentors of the next generation of cancer researchers.